Urticaria – an overview

What is urticaria?

Urticaria is characterised by weals (hives) or angioedema (swellings, in 10%) or both (in 40%). There are several types of urticaria. The name urticaria is derived from the common European stinging nettle 'Urtica dioica'.

A weal (or wheal) is a superficial skin-coloured or pale skin swelling, usually surrounded by erythema (redness) that lasts anything from a few minutes to 24 hours. Usually very itchy, it may have a burning sensation.

Angioedema is deeper swelling within the skin or mucous membranes, and can be skin-coloured or red. It resolves within 72 hours. Angioedema may be itchy or painful but is often asymptomatic.

Urticaria and angioedema

Who gets urticaria?

One in five children or adults have an episode of acute urticaria during their lifetime. It is more common in atopics. It affects all races and both sexes.

Chronic spontaneous urticaria affects 0.5–2% of the population; in some series, two-thirds are women. Inducible urticaria is more common. There are genetic and autoimmune associations.

What are the clinical features of urticaria?

Urticarial weals can be a few millimetres or several centimetres in diameter, coloured white or red, with or without a red flare. Each weal may last a few minutes or several hours, and may change shape. Weals may be round, or form rings, a map-like pattern or giant patches.

Urticaria can affect any site of the body and tends to be distributed widely.

Angioedema is more often localised. It commonly affects the face (especially eyelids and perioral sites), hands, feet and genitalia. It may involve tongue, uvula, soft palate, or larynx.

Diffuse in cold urticaria—if large areas of skin are affected, they can lead to fainting (potentially dangerous if swimming in cold water)

The weals are more persistent in chronic spontaneous urticaria, but each has gone or has altered in shape within 24 hours. They may occur at certain times of day.

Urticaria severity assessment

Visual analogue scales can be used to record and compare the degree of itch.

The activity of chronic spontaneous urticaria can be assessed using the UAS7 scoring system. The daily weal/itch scores are added up for 7 days; the maximum score is 42.

Score

Weals/24 hours

Itch

0

None

None

1

<20

Mild

2

20–50

Moderate

3

>50

Intense

The emotional impact of urticaria and its effect on quality of life should also be assessed. The Dermatology Life Quality Index (DLQI) and CU-Q2oL, a specific questionnaire for chronic urticaria, have been validated for chronic urticaria, where sleep disruption is a particular problem.

What causes urticaria?

Weals are due to release of chemical mediators from tissue mast cells and circulating basophils. These chemical mediators include histamine, platelet-activating factor and cytokines. The mediators activate sensory nerves and cause dilation of blood vessels and leakage of fluid into surrounding tissues. Bradykinin release causes angioedema.

Several hypotheses have been proposed to explain urticaria. The immune, arachidonic acid and coagulation systems are involved, and geneticmutations are under investigation.

Acute urticaria

Acute urticaria can be induced by the following factors but the cause is not always identified.

How is urticaria diagnosed?

Urticaria is diagnosed in people with a history of weals that last less than 24 hours with or without angioedema. A family history should be elicited. A thorough physical examination should be undertaken.

Skin prick tests and radioallergosorbent tests (RAST) or CAP fluoroimmunoassay may be requested if a drug or food allergy is suspected in acute urticaria.

There are no routine diagnostic tests in chronic spontaneous urticaria apart from blood count and C-reactive protein (CBC, CRP), but investigations may be undertaken if an underlying disorder is suspected.

The autologous serum skin test is sometimes carried out in chronic spontaneous urtciaria, but its value is uncertain. It is positive if an injection of the patien's serum under the skin causes a red weal.

Inducible urticaria is often confirmed by inducing the reaction, eg scratching the skin in dermographism or applying an ice cube in suspected cold urticaria.

Investigations for a systemic condition or autoinflammatory disease should be undertaken in urticaria patients with fever, joint or bone pain, and malaise. Patients with angioedema without weals should be asked if they take ACE inhibitor drugs and tested for complement C4; C1-INH levels, function and antibodies; and C1q.

Biopsy of urticaria can be non-specific and difficult to interpret. The pathology shows oedema in the dermis and dilated blood vessels, with variable mixed inflammatoryinfiltrate. Vessel-wall damage indicates urticarialvasculitis.

What is the treatment for urticaria?

The main treatment of all forms of urticaria in adults and in children is with an oral second-generation antihistamine chosen from the list below. If the standard dose (eg 10 mg for cetirizine) is not effective, the dose can be increased up to fourfold (eg 40 mg cetirizine daily). They are stopped when the acute urticaria has settled down. There is not thought to be any benefit from adding a second antihistamine.

Cetirizine

Loratadine

Fexofenadine

Desloratadine

Levocetirizine

Rupatadine

Bilastine

Terfenadine and astemizole should not be used, as they are cardiotoxic in combination with ketoconazole or erythromycin. They are no longer available in New Zealand.

Although systemic treatment is best avoided during pregnancy and breastfeeding, there have been no reports that second-generation antihistamines cause birth defects. If treatment is required, loratadine and cetirizine are currently preferred.

Conventional first-generation antihistamines such as promethazine or chlorpheniramine are no longer recommended for urticaria:

They are short-lasting.

They have sedative and anticholinergic side effects.

They impair sleep, learning and performance.

They cause drowsiness in nursing infants if taken by the mother.

They interact with alcohol and other medications.

Lethal overdoses are reported.

Avoidance of trigger factors

In addition to antihistamines, the cause of urticaria should be eliminated if known (eg drug or food allergy). Avoidance of relevant type 1 (IgE-mediated) allergens clears urticaria within 48 hours.

Treatment of refractory acute urticaria

Intramuscular injection of adrenaline (epinephrine) is reserved for life-threatening anaphylaxis or swelling of the throat.

Treatment of refractory chronic urticaria

Patients with chronic urticaria that has failed to respond to maximum-dose second generation oral antihistamines taken for 4 weeks should be referred to a dermatologist, immunologist or medical allergy specialist.

There is good evidence to support treatment with omalizumab or ciclosporin, which each have a 65% response rate in antihistamine-resistant patients.

Omalizumab is a monoclonalantibody directed against IgE, with low toxicity. Omalizumab is not funded by PHARMAC in New Zealand for urticaria (2015).

Long-term systemic corticosteroids are not recommended, as high doses are required to reduce symptoms of urticaria and they have inevitable adverse effects that can be serious.

The effectiveness of treatment can be objectively monitored using urticaria control test. Patients are asked to score the physical symptoms of urticaria they have experienced in the previous four weeks, quality of life affected by urticaria, how often treatment was not enough to control symptoms, and overall control of urticaria.

Differential diagnosis of urticaria

Papular urticaria

Insect bites are localised, often clustered in groups of 3–5 lesions, and they appear in crops. Bites persist for days. Close inspection reveals a central punctum. Chronichypersensitivity to insect bites is often called papular urticaria.

The most common form of mastocytosis, maculopapularcutaneous mastocytosis is also called urticaria pigmentosa. Itchy brown patches or freckles on the skin are due to abnormal collections of mast cells.